Biogenic amines play key roles in neurotransmission, metabolism, and in control of various physiological processes. Using a variety of synthetic methodologies, including novel procedures developed by us, we have prepared a series of biogenic amines with fluorine substituted at various ring-positions. By virtue of its very small size and high electronegativity, fluorine is a very favorable replacement for hydrogen in these analogs. The biological properties and usefulness of these ring-fluorinated biogenic amines have proved to be extremely rewarding and continue to find applications in a multitude of studies, including research on the mechanisms of transport, storage, release, metabolism, and modes of action of these amines. Of particular significance was the discovery that 6-fluoronorepinephrine is a selective alpha-adrenergic agonist and 2-fluoronorepinephrine is a selective beta-adrenergic agonist. Mechanisms considered to explain these results include: 1) a direct effect of the C-F bond on agonist-receptor interaction or 2) an indirect effect of the C-F bond on the conformation of the ethanolamine side-chain. The results of testing of new analogs synthesized to probe these mechanisms indicate that electronic effects may be more important than conformational factors. Fluorinated analogs are useful mechanistic probes and biological tracers. The increased phenol acidities of fluorinated catecholamines proved to be an effective probe for details of the mechanisms of catechol methylation by the enzyme, catechol O- methyltransferase. We now have used the increased phenol acididites of fluorinated norepinephrines to study further the relationship between pH and adrenergic activity. [18F]-labeled 6-fluorodopamine, the biological precursor to 6-fluoronorepinephrine, has been found to be an excellent scanning agent for peripheral noradrenergic innervation. Research is in progress to develop central noradrenergic scanning agents based on this series.